High-Mobility Group Box 1 expression predicts survival of patients after resection of adenocarcinoma of the ampulla of Vater.

BACKGROUND: Expression of High-Mobility Group Box 1 (HMGB1), a multifunctional protein involved in DNA function as well as cell proliferation, inflammation, and the immune response, has been reported to be prognostic in several types of malignancies. However, the prognostic value of HMGB1 in ampullary cancer has not been studied. METHODS: Patients with adenocarcinoma of the ampulla of Vater who underwent R0 resection with pancreaticoduodenectomy between 2001 and 2011 were included in the present multi-institutional study. The degree of HMGB1 expression was examined in each resected specimen by immunohistochemical staining. RESULTS: A total of 101 patients were enrolled of which, 79 patients were eligible. High expression of HMGB1 was observed in 31 (39%) patients. Blood loss, transfusion, tumor stage, nodal status, and HMGB1 expression were identified as predictors with univariate analysis. Multivariate analysis showed that transfusion, lymph-node metastasis, and high HMGB1 expression were independent predictors of poor overall survival. Subgroup analysis showed that high HMGB1 expression was predictive, especially in patients who did not receive adjuvant chemotherapy. CONCLUSIONS: High HMGB1 expression is an independent predictor of poor prognosis in patients with adenocarcinoma of the ampulla of Vater not treated with adjuvant chemotherapy.

Incidental Gallbladder Cancer on Cholecystectomy: Strategy for Re-resection of Presumed Benign Diseases from a Retrospective Multicenter Study by the Yokohama Clinical Oncology Group.

BACKGROUND/AIM: Current expert consensus recommends re-resection for incidental gallbladder cancer (IGBC) of pT1b-3. This study examined whether this consensus was reasonably applicable to patients with IGBC in one Japanese region. PATIENTS AND METHODS: This was a multicenter, retrospective analysis of cholecystectomies for presumed benign diseases between January 2000 and December 2009. RESULTS: IGBC was diagnosed in 70 (1.0%) out of 6,775 patients undergoing cholecystectomy. Five-year disease-specific cumulative survival was 100% in 19 patients with pT1a, 80.0% in five with pT1b, 49.5% in 33 with pT2, and 23.1% in 13 with pT3. Re-resection was not performed for the 24 patients with pT1a/1b disease, whereas 24 out of 46 patients with pT2/3 underwent re-resection. Regardless of re-resection, independent factors associated with a poor prognosis on multivariate analysis were grade 2 or poorer disease and bile spillage at prior cholecystectomy. In the 24 patients with pT2/3 re-resection, 11 patients without either of these two factors had significantly better 5-year disease-specific cumulative survival than the 13 patients with one or two independent factors associated with a poor prognosis (72.7% vs. 30.8%, p=0.009). CONCLUSION: This Japanese regional study suggests that indication of re-resection for IGBC should not be determined by pT-factor alone and that much more attention should be paid to pathological and intraoperative findings at prior cholecystectomy.

Usefulness of a selective neutrophil elastase inhibitor (sivelestat) in septic ARDS patients after gastrointestinal surgery.

BACKGROUND/AIMS: The usefulness of a neutrophil elastase inhibitor (sivelestat) was evaluated for treating septic acute respiratory distress syndrome (ARDS) after gastrointestinal surgery. METHODOLOGY: The subjects were 36 patients with septic ARDS after gastrointestinal surgery. ARDS was defined as acute lung injury associated with systemic inflammatory response syndrome. Sivelestat was intravenously administered at a dose of 0.2 mg/kg/hr continuously for 3 days or more. The effectiveness of sivelestat was evaluated based on the lung injury score, P/F ratio, and ventilator free days (VFD). RESULTS: Marked responses were observed in 12 patients (33.3%), responses in 17 (47.2%), and no response in 7 (19.4%). In the patients with marked responses or responses (responders), the P/F ratio was significantly improved on day 3 of drug administration and at the end of administration compared with the pre-administration ratio. Comparison between the responders and non-responders showed significant differences on day 3 and at the end of drug administration. VFD significantly differed between the responders (18.8 days) and the non-responders (11.0 days). CONCLUSION: In conclusion, sivelestat may be effective against septic ARDS. The effectiveness of the drug could be determined based on improvement in oxygenation ability on day 3 of drug administration.

Histopathological and immunohistochemical findings in a case of glycogen-rich clear cell carcinoma of the breast.

Glycogen-rich clear cell carcinoma (GRCC) of the breast is a rare variant of primary breast carcinoma that was first described by Hull et al. in 1981, and is characterized by carcinoma cells containing an optically clear cytoplasm and intracytoplasmic glycogen. The present case involved a 33-year-old female. She had noticed a lump in the inner quadrant of the left breast. The tumor obtained by enucleation biopsy had an irregular shape. The tumor cells exhibited sharply defined borders, polygonal contours, a clear or finely granular cytoplasm, and moderate nuclear atypia. The tumor cells showed a positive reaction with periodic acid Schiff, eliminated by diastase digestion. The tumor was diagnosed as GRCC. There was no nodal metastasis. Immunohistochemically, the tumor cells were positive for cytokeratin, epithelial membrane antigen, HER2, and p53, but negative for estrogen receptor (ER) and progesterone receptor (PR). Although the biological behavior of GRCC is difficult to predict in view of the very limited number of case reports, the prognosis of GRCC may be associated with not only histopathological subtype but also other clinicopathological factors, such as size, status of invasion, status of nodal metastasis, nuclear grade, ER, PR, HER-2, p53 and so on. To clarify the pathogenesis of mammary GRCC, the systematic study of additional well-documented cases with long-term follow up will be necessary.

[Two cases of parasitic granuloma found incidentally in surgical specimens].

Occasionally, parasitosis demonstrates no clinical symptoms, and is found incidentally. We report 2 cases of parasitic granuloma found incidentally in surgical specimens in rare sites for parasitosis. Case 1 was a 40-year-old female. She was diagnosed with inguinal hernia, and operation was performed. A white nodule, measured 1.5 x 1 x 1 cm in size, was found in the hernia sac. The nodule was elastic hard and solid. Histologically, eosinophilic granuloma was demonstrated, and the parasite was characterized by renette cell and Y-shaped lateral cord, and suggesting extra-gastrointestinal anisakiasis. Case 2 was a 71-year-old female. She was diagnosed with colonic adenocarcinoma, and colectomy was performed. A white nodule, measured 1 x 1 x 0.8 cm in size was found in the omentum, at first identified as peritoneal dissemination of colonic carcinoma. However, histological findings of the nodule showed eosinophilic granuloma, and parasite was observed in the granuloma. The parasite was characterized by thick cuticle and muscular cells, and suggestive of dilofilariasis. In each case, no clinical symptoms of parasitosis were recognized, and each lesion presented in a rare site as anisakiasis or dirofilariasis. When any lesions as in the present cases is found in a surgical specimen, it is important to make differential diagnosis with consideration for parasitic granuloma.

Macroscopic type is a prognostic factor for recurrence-free survival after resection of gastric GIST.

BACKGROUND: Accurate evaluation of the biological behavior of Gastrointestinal stromal tumor and careful selection of patients with a high risk for tumor recurrence are necessary. In the present study, we analyzed prognostic factors in patients with GIST. PATIENTS AND METHODS: A total of 214 patients who had undergone curative resection of a localized primary gastric GIST without adjuvant therapy were enrolled in this retrospective study. Prognostic factors were analyzed. The growth pattern was classified as intramural, endoluminal, exoluminal, or mixed- type. RESULTS: On univariate and multivariate analyses, recurrence was predicted by exoluminal or mixed-type (hazard ratio [HR]=3.7, p=0.043), tumor size of >3.5 cm (HR=7.1, p=0.01), and mitotic rate of >5/50 high-power fields (HR=7.9, p<0.001). CONCLUSION: It is suggested that exoluminal or mixed-type is independently associated with recurrence of surgically resected gastric GIST in addition to tumor size and mitotic rate.

Phase II study of biweekly docetaxel and S-1 combination chemotherapy as first-line treatment for advanced gastric cancer.

PURPOSE: We evaluated the efficacy and toxicity of biweekly S-1 and docetaxel combination therapy in patients with advanced gastric cancer. METHODS: Patients with histologically proven, unresectable advanced or recurrent gastric cancer, a performance status (PS) of 0-2 and no prior chemotherapy history were eligible for inclusion (n = 45). Patients received a total of 215 treatment courses (median, 4; range, 2-12) of S-1 oral administration twice daily for 1 week followed by a drug-free interval of 1 week. Docetaxel (40 mg/m(2)) was administered intravenously on days 1 and 15. RESULTS: We observed 25 partial responses (55.6%) and one complete response (2.2%), resulting in an overall response rate of 57.8%. Twenty-four patients (53.3%) received second-line chemotherapy. Five patients (11.1%) underwent R0 gastrectomy during the course of the study. The median overall survival time was 15.3 months, the median time to progression was 6.9 months, and the median duration of response in 26 patients was 8.0 months. Neutropenia was the most frequently observed (40.4%) haematological toxicity at grades 3 and 4 and leucopenia was the second most common (29.8%). There were no treatment-related deaths. CONCLUSIONS: S-1 plus docetaxel combination therapy in an outpatient setting provided promising activity with acceptable adverse toxicities.